Variant 15-86143818-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001386094.1(AGBL1):c.235C>T(p.Arg79Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,613,814 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R79Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 19 hom. )

Consequence

AGBL1
NM_001386094.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.28

Variant links:

Genes affected

AGBL1 (HGNC:26504): (AGBL carboxypeptidase 1) Polyglutamylation is a reversible posttranslational modification catalyzed by polyglutamylases that results in the addition of glutamate side chains on the modified protein. This gene encodes a glutamate decarboxylase that catalyzes the deglutamylation of polyglutamylated proteins. Mutations in this gene result in dominant late-onset Fuchs corneal dystrophy. [provided by RefSeq, Nov 2013]

AGBL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009001464).

BP6

Variant 15-86143818-C-T is Benign according to our data. Variant chr15-86143818-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645663.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-86143818-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd at 360 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL1	NM_001386094.1 linkuse as main transcript	c.235C>T	p.Arg79Trp	missense_variant	3/23	ENST00000614907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3 linkuse as main transcript	c.235C>T	p.Arg79Trp	missense_variant	3/23	5	NM_001386094.1	P4
AGBL1	ENST00000441037.7 linkuse as main transcript	c.235C>T	p.Arg79Trp	missense_variant	3/25	5		A2

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

360

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00911

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00273

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00316

AC:

785

AN:

248650

Hom.:

AF XY:

0.00383

AC XY:

517

AN XY:

134874

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.00290

Gnomad ASJ exome

AF:

0.00378

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.00916

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.00294

Gnomad OTH exome

AF:

0.00431

GnomAD4 exome

AF:

0.00254

AC:

3710

AN:

1461496

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

2041

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00302

Gnomad4 ASJ exome

AF:

0.00448

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.00858

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00221

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.00237

AC:

361

AN:

152318

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00458

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00932

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00273

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00237

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000251

AC:

ESP6500EA

AF:

0.00288

AC:

ExAC

AF:

0.00309

AC:

373

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00393

EpiControl

AF:

0.00362

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

AGBL1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

D;.

MetaRNN

Benign

0.0090

T;T

MetaSVM

Benign

-0.81

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

REVEL

Uncertain

0.35

Polyphen

1.0

.;D

MVP

0.54

MPC

0.064

ClinPred

0.044

GERP RS

0.75

Varity_R

0.18

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over